Method and apparatus for stent deployment with enhanced delivery of bioactive agents

ABSTRACT

A stent for use in animals including humans is disclosed which includes unprotected and protected regions, each protected regions including a bioactive or biopenetrating agent containing therein where the protected regions are protected by the unprotected regions when the stent is in its undeployed state which has a smaller cross-sectional dimension than the stent in its deployed state. And when the stent is in its deployed state the bioactive or biopenetrating agent(s) are brought into direct and intimate contact with a tissue or interior of a blood vessel of an animal including a human.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a stent including indentations having eitherbioactive agents and/or penetrating structures and/or agents therein orthereon where the indentations protect the agents or structures duringstent positioning and where the agents or structures are brought intoclose proximity to or in contact with a vessel's interior or tissueduring stent deployment.

More particularly, this invention relates to a corrugated stent havingrecessed regions containing bioactive or penetration agents orstructures and non-recessed regions, where the agents are protected inthe recessed regions. Preferably, the stent undergo a volumericexpansion after deployment, that brings the bioactive or penetrationagents or structures into close proximity to or direct contact with a avessel's interior or tissue during deployment.

2. Description of the Related Art

Stents are a valuable medical device designed to maintain pathway of avessel or maintain or create a tissue cavity in an animal's body in anopened condition. Numerous stents have been described such as those inU.S. Pat. Nos. 5,197,977, 5,282,847, 5,380,299, 5,383,927, 5,464,450,5,500,013, 5,607,464, 5,624,411, 5,653,745, 5,769,8835, and 5,776,184,incorporated herein by reference. However, these stents lack bioactiveor penetrating agents to assist in vessel or tissue healing or depositdigestion, and/or mechanisms for the protection of bioactive orpenetrating agents during stent deployment and positioning.

Thus, there is a need in the art for an improved stent having bioactiveor penetrating agents deposited thereon in such a way as to protect theagents during deployment and placement and capable of bringing theagents into close proximity or direct contact with a vessel's and/ortissue interior after deployment and expansion.

SUMMARY OF THE INVENTION

The present invention provides stents for treating, expanding and/orsupporting a portion of a vessel or for treating a tissue site, when thestent is inserted into the vessel or tissue site. The stents include atleast one or one or more recessed region and at least one or one or morenon-recessed region. One or more of the recessed regions can contain: 1)a bioactive composition designed to chemically or biochemically interactwith the interior of the vessel or the tissue site to cause aprophylactic and/or therapeutic effect; 2) a penetrating apparatus orstructure designed to mechanically or physically interact with theinterior of the vessel or the tissue site to cause a prophylactic and/ortherapeutic effect; or 3) a mixture or combination thereof. The stentshave a deployed and non-deployed state that can be the same ordifferent. In the deployed state, the recessed regions can remainrecessed, become essentially flush with the non-recessed regions,protrude above the non-recessed regions and/or include portions thatremain recessed relative to the non-recessed regions, protrude above thenon-recessed regions or are essentially flush with the non-recessedregions. The term essentially flush means that in the deployed state,the non-recessed and recessed regions form an essentially continuoussurface.

In one preferred embodiment, the stents of the present invention do notchange shape after deployment. In another preferred embodiment, thestents of the present invention have an expanded or deployed state andnon-expanded or non-deployed state. In the non-expanded or non-deployedstate, the stent has a smaller dimension compared to the stent in itsexpanded or deployed state. The dimension can be a cross-sectionaldimension, a length dimension or a combination thereof. When the stentis in its non-expanded or non-deployed state, the non-recessed regionsprotrude or extend above and protect the compositions and/or structurescontained in the recessed regions.

Moreover, the non-recessed regions are designed to deform, expand and/orelongate to a lesser extent during stent expansion or deployment thanthe recessed regions. On the other hand, the recessed regions aredesigned to deform, expand, elongate and/or flatten during deployment.The deformation of the recessed regions during stent deployment cancause the stent to assume a final contour, where the recessed regionsare substantially continuous with the non-recessed regions so the allportion of the deployed stent contact the tissue site or surface toapproximately the same extent. Alternatively, the stent can deploy sothat the recessed regions extend above the non-recessed regionscontacting the tissue site or surface to a greater extent than thenon-recessed regions. This deformation serves to bring the compositions,structures or combinations or mixtures thereof situated in the recessedregions into close proximity or direct contact with the tissue surfacesuch as the interior of a vessel or the tissue within a tissue site atthe site of deployment.

The present invention also provides bioerodible stents of the presentinvention having the same attributes of the stents disclosed above withthe added attribute that the stents themselves will eventually degrade,dissolve, erode, be metabolized or otherwise be gradually removed fromthe site of implantation.

The present invention also provides a method for treating, expanding orsupporting a vessel or other tissue site to achieve a given prophylacticor therapeutic result including the step of positioning a stent of thepresent invention at a desired site or position in an interior of avessel or within a tissue in the body of an animal. Once properlypositioned, the stent is expanded or deployed forcing the recessedregions to deform, expand, elongate and/or flatten. The deformation ofthe stent can cause the non-recessed regions and recessed regions to bebrought into close proximity or direct contact with the tissue siteexposing the tissue site to the compositions and/or structures containedwithin the recessed regions. Alternatively, the deformation can causethe recessed regions to protrude or extent above the non-recessedregions so that the compositions and/or structures contained within therecessed regions contact the tissue site to a greater extent than thenon-recessed region. An ordinary artisan should realized that in thisembodiment, the recessed regions in the non-deployed state have becomethe non-recessed regions of the deployed states and vis-a-versa. Thecontact between the stent recessed regions and the tissue site produce atherapeutic and/or prophylactic effect. If the stent is bioerodible, anadditional step will be the gradual removal or decomposition of stentitself.

The present invention also provides a method for treating, expanding orsupporting a tissue site to achieve a given prophylactic and/ortherapeutic result which includes positioning a stent of the presentinvention at a desired site or position in a tissue of the body of ananimal including a human. Once properly positioned, the stent isdeployed, thereby forcing the recessed regions to deform, expand,elongate and/or flatten. The deformation of the stent can cause thenon-recessed regions and recessed regions to be brought into closeproximity or direct contact with the tissue site exposing the tissuesite to the compositions and/or structures contained within the recessedregions. Alternatively, the deformation can cause the recessed regionsto protrude or extent above the non-recessed regions so that thecompositions and/or structures contained within the recessed regionscontact the tissue site to a greater extent than the non-recessedregion. An ordinary artisan should realize that in this embodiment, therecessed regions in the non-deployed state have become the non-recessedregions of the deployed states and vis-a-versa. The contact between thestent recessed regions and the tissue site produce a therapeutic and/orprophylactic effect. If the stent is bioerodible, an additional stepwill be the gradual removal or decomposition of stent itself.

The present invention further provides methods for making the stents ofthe present invention.

DESCRIPTION OF THE DRAWINGS

The invention can be better understood with reference to the followingdetailed description together with the appended illustrative drawings inwhich like elements are numbered the same:

FIG. 1A is a radial cross-sectional view of a first preferred embodimentof a stent of the present invention in its undeployed state;

FIG. 1B is a radial cross-sectional view of the stent of FIG. 1A in itsdeployed state;

FIG. 1C is a side view of the stent of FIG. 1A in its deployed state;

FIG. 1D is a radial cross-sectional view the stent of FIG. 1A in itsundeployed state positioned within a blood vessel;

FIG. 1E is a radial cross-sectional view the stent of FIG. 1A in itsdeployed state now engaging an interior of the blood vessel;

FIG. 2A is a radial cross-sectional view of a second preferredembodiment of a stent of the present invention in its undeployed state;

FIG. 2B is a radial cross-sectional view of the stent of FIG. 2A in itsdeployed state;

FIG. 2C is a side view of the stent of FIG. 2A in its deployed state;

FIG. 2D is a radial cross-sectional view the stent of FIG. 2A in itsundeployed state positioned within a blood vessel;

FIG. 2E is a radial cross-sectional view the stent of FIG. 2A in itsdeployed state now engaging an interior of the blood vessel;

FIG. 3A is a radial cross-sectional view of a third preferred embodimentof a stent of the present invention in its undeployed state;

FIG. 3B is a radial cross-sectional view of the stent of FIG. 3A in itsdeployed state;

FIG. 3C is a side view of the stent of FIG. 3A in its deployed state;

FIG. 3D is a radial cross-sectional view the stent of FIG. 3A in itsundeployed state positioned within a blood vessel;

FIG. 3E is a radial cross-sectional view the stent of FIG. 3A in itsdeployed state now engaging an interior of the blood vessel;

FIG. 4A is a radial cross-sectional view of a fourth preferredembodiment of a stent of the present invention in its undeployed state;

FIG. 4B is a radial cross-sectional view of the stent of FIG. 4A in itsdeployed state;

FIG. 4C is a side view of the stent of FIG. 4A in its deployed state;

FIG. 4D is a radial cross-sectional view the stent of FIG. 4A in itsundeployed state positioned within a blood vessel;

FIG. 4E is a radial cross-sectional view the stent of FIG. 4A in itsdeployed state now engaging an interior of the blood vessel;

FIG. 5A is a radial cross-sectional view of a fifth preferred embodimentof a stent of the present invention in its undeployed state;

FIG. 5B is a radial cross-sectional view of the stent of FIG. 5A in itsdeployed state;

FIG. 5C is a side view of the stent of FIG. 5A where the stent is nottwisted axially;

FIG. 5D is a side view of the stent of FIG. 5A where the stent istwisted axially into a helical configuration;

FIG. 6A is a radial cross-sectional view of a sixth preferred embodimentof a stent of the present invention in its undeployed state;

FIG. 6B is a side view of the stent of FIG. 6A in its undeployed state;

FIG. 6C is an axial cross-sectional view the stent of FIG. 6A in itsundeployed state;

FIG. 6D is a radial cross-sectional view of the stent of FIG. 6A in itsdeployed state;

FIG. 6E is an axial cross-sectional view the stent of FIG. 6A in itsdeployed state;

FIG. 7A is a side view of a seventh preferred embodiment of a stent ofthe present invention in its non-deployed state;

FIG. 7B is a side view of the stent of FIG. 7A in its undeployed state;

FIG. 8A is a radial cross-sectional view of a eight preferred embodimentof a stent of the present invention in it undeployed state;

FIG. 8B is a side view of the stent of FIG. 8A in its deployed state;

FIG. 9A is a radial cross-sectional view of a ninth preferred embodimentof a stent of the present invention in its undeployed state;

FIG. 9B is a radial cross-sectional view of the stent of FIG. 9A in itsdeployed state;

FIG. 9C is a side view of the stent of FIG. 9A in its deployed state;

FIG. 9D is a radial cross-sectional view the stent of FIG. 9A in itsundeployed state positioned within a blood vessel;

FIG. 9E is a radial cross-sectional view the stent of FIG. 9A in itsdeployed state now engaging an interior of the blood vessel;

FIG. 10A is a radial cross-sectional view of a ninth preferredembodiment of a stent of the present invention in its undeployed state;

FIG. 10B is a radial cross-sectional view of the stent of FIG. 10A inits deployed state;

FIG. 10C is a side view of the stent of FIG. 10A in its deployed state;

FIG. 10D is a radial cross-sectional view the stent of FIG. 10A in itsundeployed state positioned within a blood vessel; and

FIG. 10E is a radial cross-sectional view the stent of FIG. 10A in itsdeployed state now engaging an interior of the blood vessel.

DEFINITIONS

The term vessel means any vessel or vessel like structure in an animal(including humans) including, without limitation, ureter, airways,pancreatic ducts, biliary ducts, lymphatics, arteries, veins or othervessel type structures in the body.

The term animal means any organism that is a member of the animalkingdom including, without limitation, mammals including humans.

The term gradient means a change in some property over a givencross-section of a composition or article. The property can be, withoutlimitation, the concentration of one or more compounds, physicalstructures, compositional make-up, permeability, porosity, or any otherproperty of a composition or a structure. A gradient can vary smoothly,can includes one or more peaks, can be vary continuously, discretely ordiscontinuously across a given cross-section. A gradient peaks when theproperty has relative maxima in specific regions of the composition orstructure across some cross-section.

DETAILED DESCRIPTION OF THE INVENTION

The inventors have found that a stent can be constructed that, in itsundeployed state, include at least one zone, region, volume or area thatprotects something deposited in or on, contained in or on, or affixed toor within, positioned in or on, such as, without limitations, bioactiveagents or compositions, penetration structures and/or mixtures orcombination thereof at least one recessed region of the stent. Thecompositions and/or structures lie below and are protected by at leastone non-recessed region of the stent so that during deployment thecompositions and/or structures are protected against contact with thedeployment tools or the interior of vessels or tissue sites prior tobeing properly positioned for final deployment.

Generally, deployment involves dimensional or volumetric expansion ofthe stent at its site of deployment in a body such as in a vessel ortissue site. The dimensional or volumetric expansion can occur in boththe non-recessed and recessed regions to the same or different extent.In a preferred embodiment, the expansion occurs primarily in therecessed regions. The expansion can be radial, axial or a combination ofradial and axial. In preferred embodiments, the expansion occurssubstantially radial or substantially axial. The expansion causes therecessed regions to become accessible and/or more accessible to the siteof deployment so that, in the final stent shape, the composition and/orstructures are brought in close proximity to or into direct contact withthe site of deployment. The proximity or contact allows the compositionsand/or the structures to impart the desired prophylactic and/ortherapeutic effect at the site of deployment.

Broadly, the stents of the present invention have an elongate shape,i.e., the stents generally have an axial dimension that is greater thentheir radial dimension. One unique feature of the stents of the presentinvention are the presence of at least one recessed region and onenon-recessed region in the stent in its non-deployed state that forms aprotected zone or volume in which composition and/or structures can beintroduced that will impart a desired prophylactic and/or therapeuticeffect at the site of deployment. Preferably, the stent includes aplurality of recessed, non-recessed regions and a plurality of protectedregions, zones, areas or volumes into which composition and/orstructures can be introduced that will impart a desired prophylacticand/or therapeutic effect to a site of deployment after stentdeployment. The recessed and non-recessed regions of the stent formprotected zones in the stent. These zone can extend radially, axially ormixtures or combinations of radial or axial zones. The zones aredesigned to be filled with or contain bio-active compositions and/orstructures. The compositions and/or structures can be, withoutlimitation, affixed to the stent in the zones, formed in the zones,deposited in the zones, contained in the zones, or mixtures orcombinations thereof.

The stents also have a non-deployed and deployed state, where an overallshape of the stents changes when transitioning from its non-deployed toits deployed state resulting in the deprotection and/or exposure of thecompositions and/or structure situated within the recessed regions ofthe stent. Generally, the shape change involves a volumetric expansionof the stents after deployment, i.e., the volume of the stent in itsnon-deployed state is smaller than its volume in its deployed state. Ifthe change in volume is primarily due to a radial expansion of thestent, then the radial cross-sectional area of the stent in itsnon-deployed state is less than its deployed radial cross-sectionalarea. If the change in volume is primarily due to an axial expansion(elongation), then the length of the stent in its non-deployed state isless than its length in its deployed state. And if the stent expandsboth radially and axially, then its radial cross-sectional area andlength both increase after deployment. However, the stents can also beconstructed so that their volume or overall shape remains substantiallythe same, except that the non-recessed regions of the non-deployed stentbecome the recessed regions of the deployed stent and vis-a-versa.

In one preferred embodiment, the non-recessed regions are more rigid andnon-deformable than the recessed regions of the stent. In this preferredconfiguration, the non-recessed regions substantially maintain theirshape during stent expansion; while the recessed regions undergodeformation sufficient to deprotect the compositions and/or structuressituated within the protected zones allowing the bio-active compositionsand/or structures to affect their prophylactic and/or therapeutic effectat the site of deployment after deployment. One simple manufactureprocess for imparting differential deformation resistances to therecessed and non-recessed regions of a stent is to make the stentthicker at the non-recessed regions than at the recessed regions.

Broadly, the method of deployment of the stents of the present inventionincludes positioning a stent of the present invention at a desired sitein a body of an animal in its non-deployed state and deploying the stentat the site, where deployment causes the stent to undergo a volumetricexpansion bringing the compositions and/or structures within theprotected regions or zones in close proximity to or into direct contactwith the site. If the stent is to be deployed in a vessel, then themethod includes forming an opening in the vessel, positioning the stentwithin the vessel at a desired site, and deploying the stent at thatsite. If the stent is to be deployed in a tissue or organ, then themethod includes forming an opening in the tissue or organ, positioningthe stent within the tissue or organ at a desired site, and deployingthe stent at that site. Alternatively, the stent can simply be insertedinto the tissue or tissue site and deployed. Generally, the stent isfirst placed or positioned in a medical instrument which maintains thestent in its non-deployed state and allows for positioning of the stentat a desired site within a vessel, tissue or organ of an animal body.One preferred embodiment of this invention relates to an elongatedstructure having a corrugated radial cross-section including axiallydisposed peaks (non-recessed regions) and valleys (recessed regions),where the valleys are filled with the compositions and/or structures toa position below the tops of the peaks. Another preferred embodimentincludes an elongated structure having a pleated radial cross-sectionincluding axially disposed peaks and valleys, where the valleys arefilled with the compositions and/or structures to a position below thetops of the peaks. In these two embodiments, the peaks and valleys canbe disposed in a purely axial fashion or the structure can be twisted sothat the peaks and valleys can appear as helices.

Another preferred embodiment includes an elongated structure havingpeaks and valleys disposed radially, where the valleys are filled withthe compositions and/or structures to a position below the tops of thepeaks.

Another preferred embodiment includes an elongated structure that isunder tension in its non-deployed state and relaxed in its deployedstate, such that the bioactive composition and/or structures aresubstantially hidden in the non-deployed state and accessible in thedeployed state. In this latter embodiment, the hidden or protectedregions or zones can be disposed axially or radially.

Moreover, the stent itself can degrade and eventually disappear.

In any embodiment, composition including bioactive agents and/orstructure including penetrating agents can be situated in the protectedzones of the stent. The compositions and/or structures can be situatedwithin the protected regions by, without limitation, coating, adhering,forming, extruding, dipping, deposited in the protected zones. Theprotected zones or regions can be, without limitation, indentations,valleys, pockets, or the like or mixtures combination thereof. As thestent is inserted inside a vessel, tissue site or organ, these recessedor protected regions are shielded from mechanical removal, abrasion orrubbing due to contact with the vessel(s) and/or tissue during delivery.For use in the heart, the stents are generally delivered via the femoralartery, and normally must traverse plaque laden coronary arteries beforethey reach the site of deployment. Thus, by placing or situating thebioactive compositions and/or structures within the protected regions ofthe stent, but below the non-recessed regions of the stent or in regionshidden in the non-deployed state, the loss of bioactive compositionsand/or structures during deployment is reduced and an improved deliveryof bioactive compositions and/or structures to the site of treatment isachieved.

Once the site of treatment or deployment is reached, the stent isdeployed and assumes its deployed shape which may involve a volumetricexpansion, radial and/or axial, or simply a change in the regions of thestent that are exposed and accessible. If the stent undergoes avolumetric expansion, then such an expansion can occur in all regions ofthe stent to the same or different extent or can occur primarily in therecessed regions. Regardless, of the final deployed shape of the stent,the final shape or state exposes or further exposes the compositionsand/or structures situated in the recessed and brings them in closeproximity to or into direct contact with the vessel interior or thetissue at the site of deployment. The penetrating agents or structuresare designed to cut, abrade, serrate, break, perforate, puncture and/orpenetrate a vessel wall, a plaque deposit in a vessel, a desiredstructure within a tissue, a tumor, a cyst, or other structure withinthe body of an animal. The structures can also be designed to dislodge,dissolve, remove and/or eliminated a desired structure within the bodyof an animal. Examples of penetrating agents can include plaquedissolving chemicals (e.g., collegenase, elastase, etc.), and mechanicalstructures (e.g., metal, plastic, bioerodible polymers, micro or nanoelectromechanical systems, device or apparatus, nano-structures withbiological effects, chemical effects, mechanical effects, electricaleffects or mixtures thereof, etc.) situated in the protected regions ofthe stent or mounted within the protected regions of the stent. If thestructure is an electromechanical apparatus, system or device, then thestructure could undergo oscillatory motion allowing the structure toabrade or grind away a structure such as a plaque deposit. Theoscillatory motion could be powered by an internal power source or thestructure could include an antenna for absorbing power from an externalfield similar to the manner in which passive tagging devices are made asdescribed in U.S. Pat. Nos. 6,192,279; 6,120,460; and 5,820,589,incorporated herein by reference with respect to the electronics neededfor external field activation of a remote electromechanical device. Ifthe structure includes an electric field alignable microcrystals such ascrystals used in piezoelectric transducers, an oscillatory electricfield would cause the crystals to undergo an oscillatory motion to grindor abrade a given structure in the body such as a plaque deposit. Theelectric field could also cause movement of DNA or proteins off thestent into the tissue since DNA and proteins are charged structures. Ofcourse, because electric and magnetic fields are coupled mathematicallyby Maxwell's equations, magnetic fields can also be used.

One preferred agent delivery system involves the use of encapsulatedplaque dissolving chemicals. Upon stent deployment, the capsules aredesigned to rupture and deposit the agents onto the plaque. Anotherembodiment involves the use of metal or biodegradable structures topenetrate the plaque. These plaque penetrating structures preferablyhave a profile smaller than the height of the non-recessed areas of thestent and are generally situated in the protected zone near a center ofthe recessed regions. After deployment, the structures generally extendabove the non-recessed regions of the stent so that the structures havea greater opportunity to directly contact or protrude into the plaque.The penetrating structures may be microporous so that the structure cancontain drugs, genes or other prophylactic and/or therapeutic agents andmay be a micro or nano structures including micro and nano mechanical,electrical, electro-mechanical, etc. structures. Another embodimentinvolves the rapid or gradual release of bioactive agent (drugs, genes,growth factors and/or growth factor inhibitors) through the use ofencapsulated beads, biodegradables or other materials situated withinthe protected regions or contained within the material of the entirestent.

The inventors have found that compositions deposited or otherwisesituated or positioned in the protected regions or portions of thestents can be any composition provided that the composition is broughtinto proximity, preferable close proximity, or into contact, preferablydirect contact, with a vessel's interior surface or tissue of a tissuesite after stent deployment. The term proximity means sufficiently closeto a desired site that the composition can impart the desiredprophylactic and/or therapeutic effect to the site. The term closeproximity means sufficiently close to the desired site that thecomposition can impart substantially the entire desired effect at or tothe desired site.

The compositions can have substantially uniform, variable and/ordifferential permeability and/or porosity and/or height. Thecompositions can be permeable to bodily fluids in general or toconstituents thereof. Moreover, the permeability can vary across adesired profile of the composition or throughout the entire composition,i.e., the composition have a permeability gradient across a desiredprofile of the composition. Additionally, the compositions can haveporosities that also vary across a desired profile of the composition orthroughout the entire composition, i.e., the composition have a porositygradient across a desired profile of the composition. Compositionpermeability (or permeabilities to desired constituents of bodilyfluids) can range from essentially or substantially impermeable tohighly permeable to bodily fluids in general or to desired constituentsof bodily fluids. That is, the compositions may have include gradientsof pores (voids), material content, bioactive agents or the like. Thesegradients can change abruptly as in discontinuous changes in materials,smoothly so the property changes smoothly across a given profile of thecomposition or peaked where the permeability goes through maxima andminima across the profile.

Preferably, the compositions deposited in the protected zones of thestents of the present invention are encapsulated in an encapsulationmatrix which is designed to rupture during stent deployment or bioerodeafter deployment. The encapsulated compositions can simply be bioactiveagents designed to impart a desired prophylactic and/or therapeuticeffect on the site where the stent is deployed. The encapsulatedcompositions can be bioactive agents dispersed in a bioerodible matrixthat controls the release of the agents via bioerosion or degradation.The physical structures can also be encapsulated such as sharp crystals,crystalline structures, micro or nano structures, mechanical,electrical, electromechanical devices for penetrating into the interiorsurface of the vessel or into the tissue of a tissue site. Additionally,the crystals can be electrically or magnetically active so that theapplication of an oscillating external electric or magnetic field willcause the crystals to undergo alignment and dealingment with the linesof force inducing an abrading action similar to a motion of crystals inpiezoelectric transducer. Moreover, the non-crystal structures can bemagnetically or electrically active so that they will move in responseto an applied external field, e.g., oscillate in response to anoscillating field, turn in response to an external field, or undergo soother motion in response to an applied external field. Mixtures orcombinations of penetrating mechanical or physicals structure (bio ornon-bio degradable) and bioactive agents (chemicals, pharmaceuticals,enzymes, genes, or other gene delivery systems such as retroviruses,adenoviruses, viral vectors, plasmids, liposomes containing DNA or RNAor the like) can also be encapsulated so that the mechanical or physicalstructures will perforate the tissue or the interior surface of thevessel (plaque or vessel wall) improving the availability of thebloactive agents.

The compositions of this invention may further contain other materialssuch as fillers to improve the strength of the materials such as polymermatrices, materials that will aid in degradation, anti-degradants suchas anti-oxidants, biologically-active agents, colorants, chromophores orlight activated (fluorescent orphosphorescent) tags or any othermaterial that may alter or change the property of the compositions.

Another preferred form of the compositions and/or structures depositedin the protected regions or portions of the stents of the presentinvention is to coat the compositions and/or structures with abioerodible coating. After bioerosion of the coating, the compositionsand/or structures can impart their prophylactic and/or therapeuticeffect to a vessel or tissue.

Bioactive Agent

Bioactive agents or biologically-active agents which may be used aloneor in combination with bioerodible polymers include medicines,pharmaceuticals, drugs, or any suitable biologically-, physiologically-or pharmacologically-active substances which are capable of providinglocal biological or physiological activity to the interior surfaces ofvessels or to tissues of an animal, including a human, and if containedin an erodible polymer or polymer matrix are capable of being releasedfrom the polymer matrix into interior or interior surface of vesselssuch as blood vessels, bile ducts, ureters, pancreatic ducts, etc. orinto tissues.

If the biologically-active agent(s) are to be added to the polymercomposition during preparation, then the agent(s) are not altered by thepolymer, the solvent, if one is used or the preparation conditions.Generally, the agents are simply added to the polymer and the mixture isstirred to produce a homogeneous composition and if a solvent is used,the solvent is removed by any technique that does not result in thedilution, removal, degradation and/or decomposition of the bioactiveagent.

Suitable biologically-active agents also include substances useful inpreventing infection at the composition site, as for example, antiviral,antibacterial, antiparasitic, antifungal substances and combinationsthereof. The agent may further be a substance capable of acting as astimulant, sedative, hypnotic, analgesic, anticonvulsant, and the like.The compositions of this invention can contain large numbers ofbiologically-active agents either singly or in combination. Examples ofthese biologically-active agents include, but are not limited to: (1)anti-inflammatory agents such as hydrocortisone, prednisone,fludrotisone, triamcinolone, dexamethasone, betamethasone and the like;(2) anti-bacterial agents such as penicillins, cephalosporins,vancomycin, bacitracin, polymycins, tetracyclines, chloramphenicol,erythromycin, streptomycin, and the like; (3) antiparasitic agents suchas quinacrine, chloroquine, quinine, and the like; (4) antifungal agentssuch as nystatin, gentamicin, miconazole, tolnaftate, undecyclic acidand its salts, and the like; (5) antiviral agents such as vidarabine,acyclovir, ribarivin, amantadine hydrochloride, iododeoxyuridine,dideoxyuridine, interferons and the like; (6) antineoplastic agents suchas methotrexate, 5-fluorouracil, bleomycin, tumor necrosis factor, tumorspecific antibodies conjugated to toxins, and the like; (7) analgesicagents such as salicylic acid, salicylate esters and salts,acetaminophen, ibuprofen, morphine, phenylbutazone, indomethacin,sulindac, tolmetin, zomepirac, and the like; (8) local anaesthetics suchas cocaine, benzocaine, novocaine, lidocaine, and the like; (9) vaccinessuch as hepatitis, influenza, measles, mumps, rubella, hemophilus,diphtheria, tetanus, rabies, polio, and the like; (10) central nervoussystem agents such as tranquilizers, sedatives, anti-depressants,hypnotics, B-adrenergic blocking agents, dopamine, and the like; (11)growth factors such as colony stimulating factor, epidermal growthfactor, erythropoietin, fibroblast growth factor, neural growth factor,human growth hormone, platelet derived growth factor, insulin-likegrowth factor, and the like; (12) growth factor inhibitors such asinhibitors for colony stimulating factor, epidermal growth factor,erythropoietin, fibroblast growth factor, neural growth factor, humangrowth hormone, platelet derived growth factor, insulin-like growthfactor, and the like; (13) hormones such as progesterone, estrogen,testosterone, follicle stimulating hormone, chorionic gonadotrophin,insulin, endorphins, somatotropins and the like; (14) antihistaminessuch as diphenhydramine, chlorpheneramine, chlorcyclizine, promethazine,cimetidine, terfenadine, and the like; (15) cardiovascular agents suchas verapamil hydrochloride, digitalis, streptokinase, nitroglycerinepaparefine, disopyramide phosphate, isosorbide dinitrate, and the like;(16) bronchodilators such as metaproternal sulfate, aminophylline,albuterol, and the like; and/or (17) vasodilators such as theophylline,niacin, nicotinate esters, amyInitrate, minoxidil, diazoxide,nifedipine, and the like.

As the compositions biodegrades and/or bioerodes, thebiologically-active agent may be released from the matrix into theadjacent tissue fluids. The biologically-active agent can be releasedinto the surrounding tissue or bodily fluids at a controlled rate (abiodegradation of a uniform matrix), intermittently (layers of agentsand biodegradables), or a delayed time. For example, the polymer matrixmay be formulated to degrade after an effective and/or substantialamount of the biologically-active agent is released from the matrix.Release of a biologically-active agent having a low solubility in water,as for example a peptide or protein, may require the degradation ofgreater amounts of the polymer matrix to expose the agent directly tothe surrounding tissue fluids. Thus, the release of thebiologically-active agent from the matrix may be varied by, for example,the solubility of the biologically-active agent in water, thedistribution of the biologically-active agent within the matrix, or thesize, shape, porosity, solubility and biodegradability of the polymermatrix, among other factors.

The biologically-active agent may also be a substance or metabolicprecursor thereof, which is capable of promoting growth and survival ofcells and tissues, or augmenting the activity of functioning cells, asfor example, blood cells, neurons, muscle, bone marrow, bone cells andtissues, and the like, especially endothelial cells in the case ofvessels in the body. For example, the biologically-active agent may be anerve growth promoting substance, as for example, a ganglioside,phosphatidylserine, a nerve growth factor, brain-derived neurotrophicfactor, a fibroblast growth factor, and the like.

To promote tissue growth, the biologically-active agent may be either ahard or soft tissue promoting substance or combinations thereof.Suitable peptides and/or tissue growth promoting agents include, forexample, fibronectin (FN), endothelial cell growth factor (ECGF),cementum attachment extracts (CAE), human growth hormone (HGH), aPeriodontal ligament cell growth factor, fibroblast growth factor (FGF),animal growth hormones, platelet derived growth factor (PDGF), epidermalgrowth factor (EGF), protein growth factor interleukin-1 (IL-1),transforming growth factor (TGF beta-2), insulin-like growth factor II(ILGF-II), human alpha thrombin (HAT), osteoinductive factor (OIF), bonemorphogenetic protein (BMP) or protein derived therefrom, demineralizedbone matrix, and releasing factors thereof.

The biologically-active agent may also be a substance or metabolicprecursor thereof, which is capable of inhibiting or retarding growthand/or cell survival or augmenting the activity of functioning cells,especially endothelial cells. The inhibiting biologically-active agentsmay be either a hard or soft tissue inhibiting substance or combinationsthereof. Suitable agents include agents that can interfere with orinhibit the action of fibronectin (FN), endothelial cell growth factor(ECGF), cementum attachment extracts (CAE), human growth hormone (HGH),a Periodontal ligament cell growth factor, fibroblast growth factor(FGF), animal growth hormones, platelet derived growth factor (PDGF),epidermal growth factor (EGF), protein growth factor interleukin-1(IL-1), transforming growth factor (TGF beta-2), insulin-like growthfactor II (ILGF-II), human alpha thrombin (HAT), osteoinductive factor(OIF), bone morphogenetic protein (BMP) or protein derived therefrom,demineralized bone matrix, and releasing factors thereof.

Other suitable bioactive agents include, without limitation, DNA, RNA,or DNA/RNA sequences that encode for proteins involved in NO regulatorproteins and/or enzymes, VEFT or any of the other above-identifiedproteins, enzymes or the like. Additionally, the genetic material mayinclude up regulator factors or suppressor factors for changingoraugmenting the normal production of certain proteins, enzymes or thelike.

Encapsulating Bioactive Agents

Suitable encapsulating agents include, without limitation, anyencapsulating formation approved for use in the body including all ofthe biodegradable polymers mentioned previously in connection withbioactive agents. Moreover, photopolymerizable monomers capable of beingpolymerized in situ and to cover the recessed areas. Deployment wouldthen result in the rupturing of the covering. Additionally, starch andsugar based material can be used as an encapsulating covering over thecomposition and/or structures in the protected zones of the stents ofthe present invention.

Bioerodible Polymers and Polymeric Compositions

Suitable polymers for use in the present invention include, withoutlimitation, biocompatible polymers, preferably biocompatible polymersthat are biodegradable and/or bioerodible, i.e., the polymers eventuallydecompose in the body. The biodegradation and/or bioerodible can be bycellular degradation (e.g., macrophage degradation or the like),chemical degradation (e.g., enzymatic degradation), hydrolysis (e.g.,via bodily fluids such as plasma) or other cellular action and/or thedegradation or erosion can be due to degradation agents contained withinthe composition itself (e.g., embedded enzymes, depolymerization agentsor the like). Such polymeric substances include polyesters, polyamides,polypeptides and/or polysaccharides or the like.

Non-limiting examples of suitable biocompatible, biodegradable polymers,include polylactides, polyglycolides, polyfumarates, polycaprolactones,polyanhydrides, polyamides, polyurethanes, polyesteramides,polyorthoesters, polydioxanones, polyacetals, polyketals,polycarbonates, polyorthocarbonates, polyphosphazenes,polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates,polyalkylene succinates, poly(malic acid), poly(amino acids),poly(methyl vinyl ether), poly(maleic anhydride), chitin, chitosan, andcopolymers, terpolymers, or higher poly-monomer polymers thereof orcombinations or mixtures thereof. The preferred biodegradable polymersare all degraded by hydrolysis.

Typically, the polymers will either be surface erodible polymers such aspolyanhydrides or bulk erodible polymers such as polyorthoesters.Poly(l-lactic acid) (PILA), poly(dl-lactic acid) (PLA), poly(glycolicacid) (PGA), polycaprolactones, copolymers, terpolymer, higherpoly-monomer polymers thereof, or combinations or mixtures thereof arepreferred biocompatible, biodegradable polymers. The preferredbiodegradable copolymers are lactic acid and glycolic acid copolymerssometimes referred to as poly(dl-lactic-co-glycolic acid) (PLG). Theco-monomer (lactide:glycolide) ratios of the poly(DL-lactic-co-glycolicacid) are preferably between about 100:0 to about 50:50 lactic acid toglycolic acid. Most preferably, the co-monomer ratios are between about85:15 and about 50:50 lactic acid to glycolic acid. Blends of PLA withPLG, preferably about 85:15 to about 50:50 PLG to PLA, are also used toprepare polymer materials.

PLA, PlLA, PGA, PLG and combinations or mixtures or blends thereof areamong the synthetic polymers approved for human clinical use. They arepresently utilized as surgical suture materials and in controlledrelease devices, as well as in other medical and pharmaceuticalapplications. They are biocompatible and their degradation products arelow molecular weight compounds, such as lactic acid and glycolic acid,which enter into normal metabolic pathways. Furthermore, copolymers ofpoly(lactic-co-glycolic acid) offer the advantage of a large spectrum ofdegradation rates from a few days to years by simply varying thecopolymer ratio of lactic acid to glycolic acid.

To enhance bio-degradation of the polymers used in biologicalapplication, the compositions of the present invention can also includethe addition of enzymes that can facilitate the biodegradation of thepolymers used in the composition. Preferred enzymes or similar reagentsare proteases or hydrolases with ester-hydrolyzing capabilities. Suchenzymes include, without limitation, proteinase K, bromelaine, pronaseE, cellulase, dextranase, elastase, plasmin streptokinase, trypsin,chymotrypsin, papain, chymopapain, collagenase, subtilisn,chlostridopeptidase A, ficin, carboxypeptidase A, pectinase,pectinesterase, an oxidoreductase, an oxidase or the like. The inclusionof an appropriate amount of such a degradation enhancing agent can beused to regulate composition duration.

Suitable Solvents for Use in Forming the Bioactive Compositions

Suitable polymers can be combined with suitable organic solvents to formpolymeric solutions. The solubility or miscibility of a polymer in aparticular solvent will vary according to factors such as crystallinity,hydrophilicity, capacity for hydrogen-bonding and molecular weight ofthe polymer. Consequently, the molecular weight and the concentration ofthe polymer in the solvent are adjusted to achieve the desiredmiscibility and/or viscosity. Preferred polymers are those which have alow degree of crystallinity a low degree of hydrogen-bonding, lowsolubility in water, and high solubility in organic solvents.

In general, the polymers are dissolved in a suitable organic solvent.The solvent should not adversely affect the polymer or the particulatesolids and preferably should be a volatile organic solvent. The relativeamount of solvent will have a minimal effect on the structure of theproduced materials, but will affect the solvent evaporation time.

Solvents which may be used to make polymeric compositions of theinvention include, without limitation, N-methyl-2-pyrrolidone,2-pyrrolidone, C2 to C6 alkanols, propylene glycol, acetone, alkylesters such as methyl acetate, ethyl acetate, ethyl lactate, alkylketones such as methyl ethyl ketone, dialkylamides such asdimethylformamide, dimethyl sulfoxide, dimethyl sulfone,tetrahydrofuran, cyclic alkyl amides such as caprolactam,decylmethylsulfoxide, oleic acid, propylene carbonate, aromatic amidessuch as N,N-diethyl-m-toluamide, and 1-dodecylazacycloheptan-2-one.Preferred solvents according to the invention includeN-methyl-2-pyrrolidone, 2-pyrrolidone, dimethyl sulfoxide, acetone, andpropylene carbonate. Preferred solvents are simple ketones such asacetone, chlorinated hydrocarbons such as methylene chloride,chloroform, methylethylketone, or the like.

Preferred Stent Materials

Suitable materials that can be used to make the stents of the presentinvention include, without limitation, iron alloys such as stainlesssteels, titanium alloys, cobalt chrome alloys, nitinol, platinum-basedalloys, gold and gold alloys, silver and silver alloys, polyolefins suchas polyethylene, polypropylene, or the like, polyanhydride,polyorthoesters, polyurethane, polyesterurethane, polycaprolactone,polyacetal, polyethylene terephthalate or other polyesters, silicone,siloxanes, polysiloxanes, silicone rubbers, or other like siliconepolymers, polylactides/polyglycolides, nylon or other polyamides,polycarbonate, fluorinated polyolefins such as Teflon®, acrylics such aspolymethylmethacrylate, hyaluronic acid, collagens, hydroxyapatite,acellular tissue products, keratan, chitosan, other similar materials ormixtures or combinations thereof. For bioerodible stent, any of thebioerodible materials previously mentioned above can be used. Of course,the exact material should biodegrade at a rate slower to substantiallyslower than the rate of delivery of bioactive agents and/or structures.

Moreover, the stents may be a mixture of combination of material. Thus,the recessed regions may be polymeric, while the non-recessed regionsmay be metal; the recessed regions may be composed of a flexible ordeformable polymer, while the non-recessed regions may be composed of anon-flexible or non-deformable polymer.

Preferred Materials for Use in the Compositions

The compositions to be situated inside the protected zones of the stentsof the present invention are generally any bio-active agent, polymermatrix containing a bio-active agent or an encapsulated bio-active agentor a polymer matrix containing a bio-active agent or mixtures andcombinations thereof designed to achieve a given therapeutic and/orprophylactic effect at the site of deployment. The stents can include asingle bio-active agent or any number of bio-active agents andcompositions to regulate the release of these bio-active agents.

Preferred Materials for Use in the Structures

The structures to be situated inside the protected zones of the stentsof the present invention are generally any structure designed to achievea given therapeutic and/or prophylactic effect at the site ofdeployment. The structures can simply be crystals or other relativelyhard compounds or a mechanical, electrical, electromechanical device andmay be porous ro hold the bioactive agents in large quantities. Thecrystals, compounds, or devices are generally small and typically rangefrom about 1 nm in height to about 1 mm in height, preferably, fromabout 5 nm to about 500 μm in height and particularly, from about 50 nmto about 200 μm in height. The devices, compounds or crystals can alsoinclude bio-active agents that are delivered to the site of deploymentconcurrently with the action of the structures or at some timecontrolled by the structure itself, e.g., rate of degradation of thestructures, controlled opening of a cavity, or a composition associatedwith the structures, where the composition is as set forth above.Additionally structures which can be used in the stents of thisinvention include the structure set forth in U.S. Pat. No. 6,197,013,incorporated herein by reference.

Preferred Embodiments of the Stents Including Bioactive Agents

Referring now to FIGS. 1A-B, a first embodiment of a stent 100 of thepresent invention is shown in cross-section to have a generallytriangular cross-section in its un-deployed state and a generallycircular cross-section in its deployed state, respectively. The stent100 includes three convex arcuate, non-recessed regions 102 and threeconcave recessed regions 104, where the regions 102 and 104 regionsalternate. The stent 100 also includes a bioactive composition 106deposited in protected zones 108 located in the recessed regions 104,where the composition 106 outer surface 107 is below an outer surface103 of the non-recessed areas 102. The stent's cross-sectional dimensionin its undeployed state, as shown in FIG. 1A, can be inscribed in afirst circle 110 having a first diameter d₁ and after deployed, thestent assumes a substantially circular contour having a diameter d₂,where d₂ is greater than or equal to d₁.

Referring now to FIG. 1C, the stent 100 is shown in a side view wherethe non-recessed regions 102, the recessed regions 104 and thecomposition 106 contained therein run parallel down a length l of thestent 100 from a first end 112 to a second end 114.

Referring now to FIGS. 1D and E, the stent 100 is shown in itsundeployed and its deployed states, respectively, positioned within avessel 116 having an interior surface or lumen 118. After deployment ofthe stent 100 via radial expansion, the stent assumes a substantiallycircular cross-section having the diameter d₂, where d₂ is greater thanor equal to d₁. As shown in FIG. 1E, the recessed regions 104 areextended and the protected zones 108 and the compositions 106 areelongated relative to their undeployed state bringing the composition106 into contact with or proximity to the vessel's interior surface 118or increasing the exposure of the vessel to the composition 106originally contained within the protected zones 108.

Referring now to FIGS. 2A-B, a second embodiment of a stent 200 of thepresent invention is shown in cross-section to have a generally squarecross-section in its un-deployed state and a generally circularcross-section in its deployed state, respectively. The stent 200includes four substantially rigid arcuate non-recessed regions 202 andfour deformable, concave recessed regions 204 interposed between eachpair of non-recessed regions 202 so that the regions 202 and 204alternate. The stent 200 also includes a bioactive composition 206deposited in protective zones 208 associated with each recessed region204. Again, the composition 206 has an outer surface 207 that is belowan outer surface 203 of the non-recessed areas 202.

In its undeployed state, the stent 200, as shown in FIG. 2A, has a firstdiameter or cross-sectional dimension of d₁ and after deployed, thestent 200 assumes a substantially circular contour having a diameter d₂in its deployed state, where d₂ is greater than or equal to d₁.

Referring now to FIG. 2C, the stent 200 is shown in side view where thenon-recessed region 202, the recessed regions 204 and the composition206 contained therein run parallel down a length l of the stent 200 froma first end 210 to a second end 212.

Referring now to FIGS. 2D-E, the stent 200 is shown in its undeployedand its deployed state within a vessel 214 having an interior surface orlumen 216. After deployment of the stent 200 via primarily radialexpansion, a stent's cross-sectional dimension is now d₂, which isgreater than or equal to d₁, bringing the composition 206 in theelongated and flattened recessed regions 204 into contact with orproximity to the interior surface 216 of the vessel 214 or exposes agreater amount of the interior surface 216 to the composition 206.

Referring now to FIGS. 3A-B, a third embodiment of a stent 300 of thepresent invention is shown in cross-section to have a generallypentagonal (5-sided) cross-section in its un-deployed state and agenerally circular cross-section in its deployed state, respectively.The stent 300 includes five substantially rigid arcuate non-recessedregions 302 and five deformable, recessed regions 304 interposed betweeneach pair of non-recessed regions 302 so that the regions 302 and 304alternate. The stent 300 also includes a bioactive composition 306deposited in protected zones 308 associated with each recessed region304. Again, the composition 306 has an outer surface 307 that is belowan outer surface 303 of the non-recessed areas 302. The stent 300 has anundeployed or first diameter or cross-sectional dimension (largestcross-sectional dimension) d₁ and a deployed or second diameter orcross-sectional dimension (largest cross-sectional dimension) d₂, whered₂ is greater than or equal to d₁.

Referring now to FIG. 3C, the stent 300 is shown in a side view wherethe non-recessed region 302, the recessed regions 304 and thecomposition 306 contained therein run parallel down a length l of thestent 300 from a first end 310 to a second end 312.

Referring now to FIGS. 3D-E, the stent 300 is shown in its undeployedand its deployed state within a vessel 314 having an interior surface orlumen 316, respectively. After deployment of the stent 300 via primarilyradial expansion, the stent's cross-sectional dimension is now d₂, whichis greater than d₁, bringing the composition 306 in the elongated andflattened recessed regions 304 into contact with or proximity to theinterior surface 316 of the vessel 314 or exposes a greater amount ofthe interior surface 316 to the composition 306.

Referring now to FIGS. 4A-B, a fourth embodiment of a stent 400 of thepresent invention is shown in cross-section to have a generallyhexagonal (6-sided) cross-section in its un-deployed state and agenerally circular cross-section in its deployed state, respectively.The stent 400 includes six substantially rigid arcuate non-recessedregions 402 and six deformable, recessed regions 404 interposed betweeneach pair of non-recessed regions 402 so that the regions 402 and 404alternate. The stent 400 also includes a bioactive composition 406deposited in protective zones 408 associated with each recessed region404. Again, the composition 406 has an outer surface 407 that is belowan outer surface 403 of the non-recessed areas 402.

The stent 400 has an undeployed or first diameter or cross-sectionaldimension (largest cross-sectional dimension) d₁ and a deployed orsecond diameter or cross-sectional dimension (largest cross-sectionaldimension) d₂ where d₂ is greater than or equal to d₁. In thisembodiment, the compositions 406 deposited in the zones 408 remainrecessed below the non-recessed regions 402, i.e., the outer surface 407of the compositions 406 are below the outer surface 403 of thenon-recessed regions 402 even after deployment.

Referring now to FIG. 4C, the stent 400 is shown in a side view wherethe non-recessed region 402, the recessed regions 404 and thecomposition 406 contained therein run parallel down a length l of thestent 400 from a first end 410 and a second end 412.

Referring now to FIGS. 4D-E, the stent 400 is shown in its undeployedand its deployed state within a vessel 414 having an interior surface orlumen 416. After deployment of the stent 400 via primarily radialexpansion, the stent's cross-sectional dimension is now d₂, which isgreater than d₁, bringing the composition 406 in the elongated andflattened recessed regions 404 into contact with or proximity to theinterior surface 416 of the vessel 414 or exposes a greater amount ofthe interior surface 416 to the composition 406.

Referring now to FIGS. 5A-B, a fifth embodiment of a stent 500 of thepresent invention is shown in cross-section to have a generally pleatedcross-section in its un-deployed state and a generally circularcross-section in its deployed state, respectively. The stent 500includes alternating peaks or pleats 502 and deformable recessed regions504. The stent 500 also includes a bioactive composition 506 depositedin protected zones 504 within the recessed regions 504. Again, thecomposition 506 has an outer surface 507 that is below an outer surface503 of the non-recessed areas 502. The stent 500 has an undeployed orfirst diameter or cross-sectional dimension (largest cross-sectionaldimension) d₁ and a deployed or second diameter or cross-sectionaldimension (largest cross-sectional dimension) d₂, where d₂≧d₁.

Referring now to FIG. 5C, the stent 500 is shown in a side view wherethe peaks (non-recessed regions) 502, the valleys (non-recessed regions)504 and the composition 506 contained therein run parallel down a lengthl of the stent 500 from a first end 508 and a second end 510.

Alternatively, referring now to FIG. 5D, the peaks 502, the valleys 504and the composition 506 contained therein of the stent 500 are arrangedin a helical structure down the length l of the stent 500 from the firstend 508 and the second end 510 where the helix has a twist angle of θ,where θ can range from about 0° (no twist or parallel orientation) to ashigh as is commercially practicable, but generally not exceeding about120°. It should be recognized that all of the stents described in thepreferred embodiments and illustrated by the FIGS. 1A-4E can havehelically oriented recessed and non-recessed regions and that the numberof alternating recessed and non-recessed regions is limited only bymanufacturing criteria depending on the nature of the stent material.

As with the other preferred embodiments described above, afterdeployment, the pleated stent 500 via primarily radial expansion,assumes a cross-sectional dimension d₂ bringing the composition intocontact with or proximity to an interior surface of a vessel (not shown)or exposes a greater amount of the interior surface to the composition.

Referring now to FIGS. 6A-E, a sixth embodiment of a stent 600 of thepresent invention is shown in cross-section to have a generally circularcross-sectional contour in its un-deployed state and in its deployedstate, respectively. The stent 600 includes a substantially rigid outersurface 602 and an inner surface 604. Interposed between the outersurface 602 and the inner surface 604 is a bioactive composition 606.The composition 606 extends from a first surface 608 to a second surface610 which is below the outer surface 602. The outer surface 602 has adiameter of d₁ which corresponds to the o.d. of the stent 600 in itsundeployed state and the inner surface 604 has a diameter of d₂ whichcorresponds to the i.d. of the stent 600 in its undeployed state.

Referring now to FIGS. 6B and C, when applied between the inner surface604 and the outer surface 602, the composition 606 appears as a seriesof alternating bands 612 and raised bands 614 circumscribing the stent600 along an undeployed length l₁ from a first end 616 to a second end618.

Referring now to FIGS. 6D and E, the stent 600 is shown after deploymentwhere the surfaces 602 and 610 have a diameter d₃ corresponding to theo.d. of the stent 600 in its deployed state and which is greater than orequal to the diameter d₁. The inner surface 604 has a diameter of d₄after stent deployment corresponding to the i.d. of the stent 600 in itsdeployed state and is greater than or equal to the diameter d₂. Inaddition to radial expansion, the stent 600 undergoes longitudinal oraxial expansion. Thus, after deployment the length l₂ of the stent 600increase (see FIG. 6E). However, the stent 600 can be designed so thatl₂ is substantially equal to l₁. Moreover, after deployment thecompositional bands 612 elongate and expand so that their outer surface620 is brought into contact with or proximity to the interior of avessel's interior surface or with a tissue.

Referring now to FIG. 7A, a seventh embodiment of a stent of the presentinvention generally 700 is shown in a side view. The stent 700 is of ahollow, substantially cylindrical shape having a length l₁ and adiameter d₁. In its undeployed state, the stent 700 is designed to closeouter regions 702 along seams 704 which seal and protect a bioactivecomposition 706 with recessed regions 708 of the stent 700.

Referring now to FIG. 7B, the stent 700 is shown after deployment as ahollow, generally cylinder shape having a length l₂ and a diameter d₂,where l₂≧l₁ and d₂≧d₁. In its undeployed state, the stent 700 isdesigned to expand radially and longitudinally raising and exposing therecessed regions 708 thereby bringing the bioactive composition 706 intocontact with or proximity to a tissue or an interior of a vessel.

Referring now to FIGS. 8A-B, an eighth embodiment of a stent of thepresent invention 800 is shown in a cross-section in its undeployedstate (FIG. 8A) and in its deployed state (FIG. 8B). The stent 800comprises a hollow, substantially cylindrical shape having an undeployeddiameter d₁ and a deployed diameter d₂, where d₂≧d₁. The stent 800includes covering regions 802 that close along seams 804 which seal andprotect a bioactive composition 806 contained within covered regions 808of the stent 800.

In its undeployed state, the stent 800 is under tension, eithercompressive tension and/or expansive tension, so that the coveringregions 802 close at seams 804 to cover and protect the composition 806contained within the covered regions 808.

Referring now to FIGS. 8C-D, the stent 800 is shown before and afterdeployment as a hollow, generally cylinder shape having an undeployedlength l₁ and a deployed length l₂, where where l₂>l₂. In its undeployedstate, the stent 800 is designed to expand radially and longitudinallyraising and exposing the covered regions 808 thereby bringing thebioactive composition 806 into contact with or proximity to a tissue oran interior of a vessel.

Although the embodiments depicted in FIGS. 7A to 8D show the coveringregions close completely, alternate constructions include constructionswhere the stents are compressed so that in the undeployed state lesscomposition is exposed than in the deployed state. That is, when thestent is tension to its undeployed state, the covering regions do notcome into contact, but are simply brought closer together than in theirdeployed state.

Although this embodiments depicted in this section are shown either withfinal circular cross-sections or starting an final circularcross-sections, the stents can be constructed so that the initial and/orfinal cross-sectional contour is any contour that can be constructed ormanufactured or that satisfies the design criteria for deployment in agiven site in a body. Thus, the stents can have initial or finalcross-sections that are oval, polygonal (trigonal, quadrilateral,pentagonal, etc.), pleated, banded, irregular or mixtures orcombinations thereof.

If the compositions protected in the protected zones of any of thestents described in the figures above comprises a compositionencapsulated by a encapsulating material, then elongation will generallyresult in a rupture of the encapsulating material. Alternatively, if thecomposition comprises small beads or capsules surrounded byencapsulating material, then elongation will generally result in therupture of some or all of the capsules. Alternatively, the encapsulatingmaterial may be designed to degrade in a biological setting after somespecific time after deployment. Of course, the capsules can be designedto have different degradation rates so that the delivery of bioactiveagents is extended over a given period of time. Although this embodimentdescribed in the figures above include a composition contained in theprotected zones, it should be recognized that penetrating structures canalso be used in addition to or in conjunction with the compositions. Infact, the penetrating structures and compositions can be constructed sothat deployment brings the tissue site into contact first with thepenetrating structure and/or compositions. These structures would openthe tissue site so that the bioactive agents would have improvedbio-availability to a targeted site.

Preferred Embodiments of the Stents Including Penetrating Structures

Referring now to FIGS. 9A-B, an illustrative embodiment of a stent ofthe present invention 900 is shown in cross-section to have a generallyhexagonal cross-sectional profile in its un-deployed state and agenerally circular shape in its deployed state, respectively. The stent900 includes four substantially rigid arcuate non-recessed regions 902and four deformable, recessed regions 904 interposed between each pairof non-recessed region 902 so that the region 902 and 904 alternate. Thestent 900 also includes a mechanical penetrating structure 906 depositedin valleys 908 associated with each recessed region 904. The stent'scross-sectional dimension having a first diameter d, and a seconddiameter or dimension d₂ where d₂≧d₁.

Referring now to FIG. 9C, the stent 900 is shown in perspective viewwhere the non-recessed region 902, the recessed regions 904 and thestructure 906 contained therein run parallel down a length l of thestent 900 from a first end 910 and a second end 912.

Referring now to FIGS. 9D-E, the stent 900 is shown in its undeployedand its deployed state within a vessel 914 having an interior surface orlumen 916, respectively. After deployment of the stent 900 via radialexpansion, the stent's cross-sectional dimension increases to d₂ and asshown in FIG. 9F, the recessed regions 904, the valleys 908 and thestructures 906 are elongated and flattened relative to their undeployedstate and now contact and penetrate the vessel's interior 920.

Referring now to FIGS. 10A-B, an illustrative embodiment of a stent ofthe present invention 1000 is shown in cross-section to have a generallyhexagonal cross-sectional profile in its un-deployed state and agenerally circular shape in its deployed state, respectively. The stent1000 includes four substantially rigid arcuate non-recessed regions 1002and four deformable, recessed regions 1004 interposed between each pairof non-recessed regions 1002 so that the regions 1002 and 1004alternate. The stent 1000 also includes a combination mechanical orelectrocmechanical penetrating structure 1006 containing a composition1007 located in protected zones 1008 associated with each recessedregion 1004. The stent's cross-sectional dimension having a firstdiameter d₁ and a second diameter or dimension d₂ where d₂≧d₁.

Referring now to FIG. 10C, the stent 1000 is shown in perspective viewwhere the non-recessed region 1002, the recessed regions 1004 and thestructures 1006 and composition 1007 contained therein run parallel downa length l of the stent 1000 from a first end 1010 to a second end 1012.

Referring now to FIGS. 10D-E, the stent 1000 is shown in its undeployedand its deployed state within a vessel 1014 having an interior surfaceor lumen 1016. After deployment of the stent 1000 via radial expansion,the stent's cross-sectional dimension increases to d₂ and as shown inFIG. 10F, the recessed regions 1004, the protected zones 1008 and thestructures 1006 containing the composition 1007 are elongated relativeto their undeployed state and now penetrate the tissue or vessel'sinterior 1020 and delivery the bioactive agents contained within thecomposition 1007 into the tissue or vessel interior.

All references cited herein are incorporated herein by reference. Whilethis invention has been described fully and completely, it should beunderstood that, within the scope of the appended claims, the inventionmay be practiced otherwise than as specifically described. Although theinvention has been disclosed with reference to its preferredembodiments, from reading this description those of skill in the art mayappreciate changes and modification that may be made which do not departfrom the scope and spirit of the invention as described above andclaimed hereafter.

1. A stent comprising: an elongate body and a protected zone including acomposition and/or structure, where the stent has an undeployed stateand a deployed state and the zone is substantially protected when thestent is in its undeployed state.
 2. The stent of claim 1, wherein thebody further includes a plurality of protected zones.
 3. The stent ofclaim 1, further comprising a plurality of alternating non-recessed andrecessed regions, each recessed region comprising a protected zone,where the composition and/or structure is positioned below tops of thenon-recessed regions.
 4. The stent of claim 3, wherein the alternatingnon-recessed and recessed regions are oriented parallel to an axisrunning a length of the stent.
 5. The stent of claim 3, wherein thealternating non-recessed and recessed regions comprise alternating bandsoriented radially with respect to an axis running a length of the stent.6. A stent comprising: an elongate body and a protected zone including acomposition and/or structure, where the stent has an undeployed stateand a deployed state and the protected region is substantially protectedwhen the stent is in its undeployed state and the composition and/orstructure is brought into close proximity to or direct contact with asite in a body of an animal, when the stent is in its deployed state. 7.The stent of claim 6, wherein the body further includes a plurality ofprotected regions.
 8. The stent of claim 6, further comprising aplurality of alternating non-recessed and recessed regions, eachrecessed region forming a protected region, where the composition and/orstructure is positioned below tops of the non-recessed regions.
 9. Thestent of claim 8, wherein the alternating non-recessed and recessedregions are oriented parallel to an axis running a length of the stent.10. The stent of claim 8, wherein the alternating non-recessed andrecessed regions comprise alternating bands oriented radially withrespect to an axis running a length of the stent.
 11. A stentcomprising: a body and a protected zone including a composition and/orstructure and formed by two non-recessed regions and a recessed region,where the stent has an undeployed state and a deployed state and theprotected zone is substantially protected when the stent is in itsundeployed state and the composition and/or structure is brought intoclose proximity to or direct contact with a site in a body of an animal,when the stent is in its deployed state.
 12. The stent of claim 11,wherein the body is elongate.
 13. The stent of claim 11, furthercomprising a plurality of alternating non-recessed and recessed regions,each recessed region forming a protected zone and there the compositionand/or structure includes a bioactive or biopenetrating agent.
 14. Thestent of claim 13, wherein the alternating non-recessed and recessedregions are oriented parallel to an axis running a length of the stent.15. The stent of claim 13, wherein the alternating non-recessed andrecessed regions comprise alternating bands oriented radially withrespect to an axis running a length of the stent.
 16. A stentcomprising: a first end; a second end; a first cross-sectional dimensionwhen the stent is in an undeployed state; a second cross-sectionaldimension when the stent is in a deployed state; a protected zone formedbetween two non-recessed region and a recessed region, where zoneincludes a composition and/or structure positioned below tops of thenon-recessed regions, where the tops of the non-recessed region protectthe composition and/or structure during stent positioning and deploymentand during deployment the composition and/or structure is brought intoclose proximity to or direct contact with a site in an animal body. 17.The stent of claim 16, wherein the stent is elongate.
 18. The stent ofclaim 16, further comprising a plurality of alternating non-recessed andrecessed regions, each recessed region forming a protected zoneincluding composition and/or structure positioned below tops of thenon-recessed regions.
 19. The stent of claim 16, wherein the alternatingnon-recessed and recessed regions are oriented parallel to an axisrunning a length of the stent.
 20. The stent of claim 16, wherein thealternating non-recessed and recessed regions comprise alternating bandsoriented radially with respect to an axis running a length of the stent.21. A method for deploying a stent comprising the steps of: positioninga stent of claims 1, 6, 11 or 16 at a site in an animals body while thestent is in its undeployed state, where the protected zone including thecomposition and/or structure is substantially protected; and deployingthe stent in the site so that the stent assumes its deployed statebringing the composition and/or structure into close proximity to ordirect contact with to the site.
 22. A method for administering atherapeutic affect to a site of an animals body comprising the steps of:positioning a stent of claims 1, 6, 11 or 16 at a site in an animalsbody while the stent is in its undeployed states, where the protectedzone including the composition and/or structure is substantiallyprotected; and deploying the stent in the site so that the stent assumesits undeployed states and bringing the composition ans/or structure intoclose proximity to or direct contact with the site; and delivering atherapeutic affect via the composition and/or structure to the site.